Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma.

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.

Respiratory Musculature Evaluated by Computed Tomography in the Setting of Prolonged Mechanical Ventilation.

BACKGROUND: Diaphragm atrophy has been observed in subjects who undergo invasive mechanical ventilation. We propose a new method to assess for respiratory muscle (RM) changes in subjects who undergo invasive mechanical ventilation by assessing for changes in respiratory muscles through computed tomography (CT). METHODS: A retrospective case series study was conducted on subjects who underwent invasive mechanical ventilation and received at least 2 chest CT scans during admission. Exclusion criteria included history of chronic mechanical ventilation dependence and neuromuscular disease. Respiratory muscle cross-sectional area (CSA) was measured at the T6 vertebrae. RESULTS: Fourteen subjects were included: mean (± SD) age, BMI, and admission APACHE II scores were 54.0 y (± 14.9), 32.6 kg/m2 (± 10.9), and 23.5 (± 6.0), respectively. Ten (71%) subjects were male. Mean length of time between CT chest scans was 7.5 d (± 3.3). Mean duration of invasive mechanical ventilation was 4.5 d (± 3.4). The percentage change in TM CSA among those who underwent invasive mechanical ventilation was 10.5% (± 6.1). CONCLUSIONS: We demonstrated that serial analysis of respiratory muscle CSA through CT chest scans can be a method to assess for respiratory muscle atrophy in subjects undergoing mechanical ventilation. Future prospective studies involving larger populations are needed to better understand how this method can be used to predict outcomes in mechanically ventilated patients.

Predicting Non-home Discharge After Lung Surgery: Analysis of the General Thoracic Surgery Database.

BACKGROUND: Anticipating the need for non-home discharge (NHD) enables improved patient counseling and expedites placement, potentially reducing length of stay and hospital readmission. The objective of this study was to create a simple, preoperative, clinical prediction tool for NHD using The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). METHODS: The STS GTSD was queried for patients who underwent elective anatomic lung cancer resection between 2009 and 2019. Exclusion criteria included age <18 years, percentage predicted diffusion capacity of the lung for carbon monoxide <20% or >150%, N3 or M1 disease, incomplete datasets, and mortality. The primary outcome was defined as discharge to an extended care, transitional care, rehabilitation center, or another hospital. Multivariable logistic regression was used to select risk factors and a nomogram for predicting risk of NHD was developed. The approach was cross-validated in 100 replications of a training set consisting of randomly selected two-thirds of the cohort and a validation set of remaining patients. RESULTS: A total of 35 948 patients from the STS GTSD met inclusion criteria. Final model variables used to derive the nomogram for NHD risk prediction included age (P < .001), percentage predicted diffusion capacity of the lung for carbon monoxide (P < .001), open surgery (P < .001), cerebrovascular history (P < .001), and Zubrod score (P < .001). The receiver operating characteristic curve, using sensitivities and specificities of the model, yielded area under the curve of 0.74. In 100 replicated cross-validations, out-of-sample area under the curve ranged from 0.72-0.76. CONCLUSIONS: Using readily available preoperative variables, our nomogram prognosticates the risk of NHD after anatomic lung resection with good discriminatory ability. Such risk stratification can enable improved patient counseling and facilitate better planning of patients' postoperative needs.

The association between thoracic sarcopenia and survival is gender specific in early-stage lung cancer.

Background: Sarcopenia, as measured at the 3rd lumbar (L3) level, has been shown to prognosticate survival in cancer patients. However, many patients with early-stage non-small cell lung cancer (NSCLC) do not undergo abdominal imaging. We hypothesized that preoperative thoracic sarcopenia is associated with survival in patients undergoing lung resection for early-stage NSCLC. Methods: Patients who underwent anatomic resection for NSCLC between 2010-2019 were retrospectively identified. Exclusion criteria included induction therapy, less than 90 days of follow-up, and absence of computed tomography (CT) imaging. Cross sectional skeletal muscle area was calculated at the fifth thoracic vertebra (T5), twelfth thoracic vertebra (T12), and L3 level. Gender-specific lowest quartile values and previously defined values were used to define sarcopenia. Overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: Overall, 221 patients met inclusion criteria with a median body mass index (BMI) of 26.5 kg/m2 [interquartile range (IQR), 23.3-29.9 kg/m2], age of 69 years (IQR, 62.4-74.9 years), and follow-up of 46.9 months (IQR, 25.0-70.7 months). At the T5 level, sarcopenic males demonstrated worse overall survival [median 41.0 (IQR, 13.8-53.7) vs. 42.0 (IQR, 23.1-55.1) months, P=0.023] and disease-free survival [median 15.8 (IQR, 8.4-30.78) vs. 34.8 (IQR, 20.1-50.5) months, P=0.007] when compared to non-sarcopenic males. There was no difference in survival between sarcopenic and non-sarcopenic females when assessed at T5. Sarcopenia at T12 or L3 was associated with worse overall survival (P<0.05). Conclusions: Sarcopenia at T5 is associated with worse survival in males, but not females. When using upper thoracic vertebral levels to assess for sarcopenia, it is necessary to account for gender.

Evaluation of the safety and effectiveness of neoadjuvant combined chemoimmunotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective single-arm cohort study.

Background: Transforming potentially resectable advanced esophageal squamous cell carcinoma (ESCC) into resectable ESCC through preoperative induction therapy is an important component of ESCC comprehensive treatment. Immune checkpoint inhibitor (ICI) therapy has been shown to have significant effects in the treatment of advanced ESCC, but its role in the neoadjuvant treatment of potentially resectable ESCC is unclear. This study aims to investigate the safety and effectiveness of camrelizumab combined with chemotherapy in the neoadjuvant treatment of ESCC. Methods: We recruited consecutive patients with potentially resectable ESCC who received preoperative camrelizumab in combination with chemotherapy. Data including demographic data, clinicopathological characteristics, neoadjuvant treatment regimens, lesion changes observed by imaging, and surgical details were retrospectively collected through specially designed forms. Toxic effects of neoadjuvant therapy on hematology, gastrointestinal tract, liver, kidney, skin, and thyroid were also collected. Imaging assessments were performed every 1-2 treatment cycles. Follow-up is based on the patient's regular admission to the hospital for examination and treatment, at least 3 months after surgery. Results: A total of 66 patients with locally advanced ESCC were included in this study, including 8 patients with stage II, 29 patients with stage III, and 29 patients with stage IVA. The objective response rate (ORR) of the neoadjuvant immunotherapy combined with chemotherapy was 75.76% (50/66), and no one developed disease progression. A total of 60 patients underwent surgery, and the R0 resection rate was 98.3% (59/60). The pathological complete remission (pCR) rate and the major pathological response (MPR) rate was 6.7% (4/60) and 20% (12/60), respectively. There were 14 cases of treatment-related adverse reactions >3, but no perioperative deaths occurred. Conclusions: Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection may be an available treatment for patients with locally advanced ESCC.

Purse-indigitation mechanical anastomosis vs. traditional mechanical anastomosis undergoing McKeown esophagectomy: a retrospective comparative cohort study.

Background: Postoperative anastomosis-related complication rates remain high in patients undergoing McKeown esophagectomy with cervical anastomosis, and the optimal anastomotic technique remains under debate. We describe a new method of anastomosis, referred to as purse-indigitation mechanical anastomosis (PIMA) by reinforcing esophagogastric anastomosis, which can be performed after minimally invasive surgery. This study was designed to compare its feasibility, efficacy, and safety with those of traditional mechanical anastomosis (TMA). Methods: Between September 2020 and January 2022, 264 patients undergoing McKeown esophagectomy at a single center were included. Demographic data, including patient age, sex, diagnosis, neoadjuvant chemotherapy/radiation therapy in cases of malignancy, comorbidities, and operation time, anastomotic time, estimated blood loss, post­operative complications were collected. Their medical records were retrospectively reviewed, analyzed and compared between the PIMA and TMA cohorts. Results: The baseline comparability of the PIMA and TMA before the comparisons is no statistical difference. Univariable analysis revealed significantly decreased anastomotic leak rate with PIMA compared to TMA (4.10% vs. 11.59%, P=0.04). No significant difference was demonstrated in total operation time, estimated blood loss, postoperative hospital stay, or pulmonary complications between PIMA and TMA (243.94±21.98 vs. 238.70±28.45 min; 201.10±67.83 vs. 197.39±65.13 mL; 8.83±2.77 vs. 9.35±3.78 days; 8.21% vs. 11.59%; all P>0.05). The incidence of postoperative pulmonary complications (3.44% vs. 50%) was significantly associated with an increased rate of anastomotic leak [odds ratio (OR): 15.50; 95% confidence interval (CI): 4.81-43.71; P<0.01]. Conclusions: PIMA is feasible, safe to perform, and demonstrated a leak rate less than half that of TMA in this study. PIMA may represent a superior alternative to standard esophagogastric cervical anastomosis techniques. Larger sample size and long-term survival are required to fully evaluate PIMA.

Comparisons of prognosis prediction accuracy between modified and unmodified versions of 8th edition ypTNM.

Background: The prognostic value of the existing 8th edition post-neoadjuvant treatment (ypTNM) appears to be limited, and necessary reassessment and modification should be carried out as needed. This study aimed to compare the prognosis prediction accuracy of modified and unmodified versions of the 8th edition ypTNM. Methods: Esophageal cancer patients who had received neoadjuvant therapy from the Surveillance, Epidemiology, and End Results (SEER) database were included in this observational longitudinal study. The median follow-up time was 26 months. All-cause mortality was the outcome variable. Demographic and clinical variables were collected as covariates. Kaplan-Meier (log-rank test) and Cox proportional hazards models were conducted for developing modified ypTNM staging. The concordance index (C-index) was calculated to analyze the discriminative ability of modified ypTNM staging. Results: Overall, 3,595 patients met inclusion criteria. The 8th edition staging was not able to significantly discriminate between patients with ypT1- and ypT2-, ypT3- and ypT4-, ypN2- and ypN3- disease, respectively. Using the modified staging, we found that patients with ypT0-2 [hazard ratio (HR) =1.232; 95% confidence interval (CI): 1.053-1.441] and ypT3-4 (HR =1.257; 95% CI: 1.136-1.390) with grade III + IV had a significant risk of death compared to those with grade I + II. As was the case for the ypN0 (HR =1.295; 95% CI: 1.073-1.562) group with middle and upper tumor locations compared to those with low tumor location. The modified staging possessed better homogeneity in terms of the chi-square likelihood ratio (143.443 vs. 102.044), Akaike information criterion (AIC) (32,683.716 vs. 32,719.115), and Schwarz's Bayesian criterion (SBC) (32,723.496 vs. 32,741.847), as well as better discriminatory ability (C-index of 0.577 vs. 0.560, P=0.045) compared to the 8th edition staging. Conclusions: Although the modified ypTNM staging system we created by incorporating tumor grade and location to the original T and N displayed certain prognosis prediction accuracy compared with the 8th edition ypTNM staging, a larger sample size and prospective studies are needed to explore.

Concordance of Computed Tomography Regional Body Composition Analysis Using a Fully Automated Open-Source Neural Network versus a Reference Semi-Automated Program with Manual Correction.

Quick, efficient, fully automated open-source programs to segment muscle and adipose tissues from computed tomography (CT) images would be a great contribution to body composition research. This study examined the concordance of cross-sectional areas (CSA) and densities for muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intramuscular adipose tissue (IMAT) from CT images at the third lumbar (L3) between an automated neural network (test method) and a semi-automatic human-based program (reference method). Concordance was further evaluated by disease status, sex, race/ethnicity, BMI categories. Agreement statistics applied included Lin's Concordance (CCC), Spearman correlation coefficient (SCC), Sorensen dice-similarity coefficient (DSC), and Bland−Altman plots with limits of agreement (LOA) within 1.96 standard deviation. A total of 420 images from a diverse cohort of patients (60.35 ± 10.92 years; body mass index (BMI) of 28.77 ± 7.04 kg/m2; 55% female; 53% Black) were included in this study. About 30% of patients were healthy (i.e., received a CT scan for acute illness or pre-surgical donor work-up), while another 30% had a diagnosis of colorectal cancer. The CCC, SCC, and DSC estimates for muscle, VAT, SAT were all greater than 0.80 (>0.80 indicates good performance). Agreement analysis by diagnosis showed good performance for the test method except for critical illness (DSC 0.65−0.87). Bland−Altman plots revealed narrow LOA suggestive of good agreement despite minimal proportional bias around the zero-bias line for muscle, SAT, and IMAT CSA. The test method shows good performance and almost perfect concordance for L3 muscle, VAT, SAT, and IMAT per DSC estimates, and Bland−Altman plots even after stratification by sex, race/ethnicity, and BMI categories. Care must be taken to assess the density of the CT images from critically ill patients before applying the automated neural network (test method).

Textbook outcome after minimally invasive esophagectomy is an important prognostic indicator for predicting long-term oncological outcomes with locally advanced esophageal squamous cell carcinoma.

Background: The textbook outcome (TO) emerges as a novel prognostic factor in surgical oncology. The present study aimed to evaluate the effect of TO on the risk of death and recurrence in patients with esophageal squamous cell carcinoma (ESCC) after minimally invasive esophagectomy (MIE). Methods: The study involved retrospective analysis of 528 patients with ESCC who were subjected to MIE from January 2011 to December 2017. TO included 8 parameters: complete resection; microscopically tumor-negative resection margins (R0); ≥15 lymph nodes removed and examined; no serious postoperative complications; no postoperative intervention; no re-admission to the intensive care unit (ICU); hospital stay ≤21 days; and no readmission ≤30 days. The Cox and logistic regression model were used to analyze the prognostic factors of survival and risk factors for TO. Results: Among the 528 patients with ESCC who were subjected to MIE, 53.2% reached TO. In the case of patients with locally advanced ESCC, 5-year overall survival (OS) was 51.1% (41.2-61.2%) for the TO group but 33.7% (23.7-43.7%) for the non-TO group (HR =0.644, 95% CI: 0.449-0.924, P=0.015). Similarly, 5-year disease-free survival (DFS) was 47.6% (38.0-57.2%) for the TO group but 29.1% (20.1-38.1%) for the non-TO group (HR =0.671, 95% CI: 0.479-0.940, P=0.018). In addition, 5-year recurrence-free survival (RFS) was 62.9% (53.7-72.1%) for the TO group but 39.8% (29.4-50.2%) for the non-TO group (HR =0.606, 95% CI: 0.407-0.902, P=0.012). Multivariate logistic regression analysis further showed that age, American Society of Anesthesiology (ASA) score, intraoperative blood loss, and smoking status acted as independent risk factors for TO. The results of the multivariate analysis assisted in the establishment of a nomogram for the prediction of TO occurrence. This nomogram exhibited satisfactory consistency and prediction ability [area under the receiving operator characteristic (AUROC) =0.717]. Conclusions: The present study showed that achieving of TO after MIE improves survival rate and reduce the recurrence rate in patients with locally advanced ESCC. The study further determined the independent factors associated with TO achievement and established a prediction model.

Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD.

X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n = 30, 75%) and HLA-mismatched (n = 10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p = 0.01) and 8.2 (CI 2.1-32.7, p < 0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT.

Randomized Trial of Dilute Povidone-Iodine Soak and Scrub for Orthopaedic Foot and Ankle Surgery.

BACKGROUND: There is no consensus as to which skin antiseptic solution is most effective at reducing infection following orthopaedic foot and ankle surgery. The purpose of this study is to determine if the addition of a dilute povidone-iodine soak and scrub to a standard preparation with alcohol and chlorhexidine decreases positive bacterial culture rates from the hallux nailfold. METHODS: In this prospective, randomized controlled trial, 242 subjects undergoing orthopaedic foot and ankle surgery were randomized to one of 2 groups. The control group received our standard 2-step skin antiseptic preparation of an alcohol scrub (step 1) followed by chlorhexidine/alcohol paint (step 2). The intervention group received a 3-minute dilute povidone-iodine soak and scrub followed by that same standard 2-step skin preparation. Immediately before skin incision, culture swabs were taken from the hallux nailfold of both groups. RESULTS: Of the 257 subjects enrolled and randomized, 242 (94.2%) completed the study, satisfying the a priori sample size requirement of 242 subjects. There were no crossovers between groups. There were no differences in baseline characteristics between groups (P > .05 for each). There was no difference in bacterial growth rates between groups (26.8% growth in the intervention group vs 26.9% growth in the control group, P = .991). CONCLUSION: The hallux nailfold is one of the most difficult to sterilize areas prior to orthopaedic foot and ankle surgery. This randomized controlled trail found no benefit to adding a 3-minute dilute povidone-iodine soak and scrub to a standard skin preparation with alcohol and chlorohexidine. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Transfer of the Posterior Tibial Tendon for Chronic Peroneal Nerve Palsy.

¼: The common peroneal nerve (CPN) is one of the most frequently injured nerves of the lower extremity. ¼: One-third of patients who develop CPN palsy proceed to chronic impairment without signs of recovery. ¼: Ankle-foot orthoses can provide improvement with respect to gait dysfunction and are useful as a nonsurgical treatment option. ¼: Severe cases of CPN palsy demonstrating no signs of recovery may require operative intervention with tendon transfer.

Cannabis Use Is Associated With Recurrence After Primary Spontaneous Pneumothorax.

Purpose: Primary spontaneous pneumothorax (PSP) is a frequently encountered entity that carries a high rate of recurrence. The current study aims to investigate if cannabis use at time of initial PSP is associated with disease recurrence. Methods: Patients presenting with PSP between 2010 and 2018 at a single institution were identified. Exclusion criteria included secondary pneumothorax, severe chronic lung disease, lung cancer, and lost to follow-up. Patients were compared relative to their cannabis usage with Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. Results: Overall, 67 patients (53 male) met inclusion criteria with a median body mass index (BMI) of 21.5 kg/m2 (IQR 19.1-25.2) and age of 34 years (IQR 22-53). Initial treatment consisted of chest tube in 42 patients (63%), video-assisted thoracoscopic surgery wedge resection in 19 patients (28%), and observation in 6 patients (9%). Cannabis users (n = 28; 42%) had a higher rate of tobacco use (79 vs. 38%; p = 0.005), lower BMI [21.0 kg/m2 (IQR 18.3-23.1) vs. 22.2 kg/m2 (IQR 19.9-28.6), p = 0.037], and were more likely to require intervention at first presentation compared with non-marijuana users. Cannabis use was associated with PSP recurrence when adjusting for tobacco use, BMI, and height (OR 1.85, 95% CI 1.38-18.3, p = 0.014). Conclusion: There is a high rate of cannabis usage in patients presenting with PSP. Cannabis usage is associated with PSP recurrence and eventual need for operative intervention.

Novel application of respiratory muscle index obtained from chest computed tomography to predict postoperative respiratory failure after major non-cardiothoracic surgery.

BACKGROUND: Postoperative respiratory failure (PRF) is a serious complication associated with significant morbidity and mortality. We propose a new method to predict PRF by utilizing computed tomography (CT) of the chest to assess degree of respiratory muscle wasting prior to surgery. METHODS: Patients who received a chest CT and required invasive mechanical ventilation (MV) after major non-cardiothoracic surgery were included. Exclusion criteria included cardiothoracic surgery. Respiratory muscle index (RMI) was calculated at the T6 vertebra measured on Slice-O-Matic® software. RESULTS: Thirty three patients met inclusion with a mean (±SD) age, BMI, and APACHE II score of 62.2 years (±12.1), 28.1 kg/m2 (±7.8), and 14.1 (±4.7). Most patients were female (n = 22 [67%]). Eleven patients (33%) developed PRF with a mean of 6.0 (±10.7) initial ventilation days. There was no difference in baseline demographics between groups. RMI values for the PRF group were significantly lower when compared to the non-PRF group: 22.7 cm2/m2 (±5.3) vs. 28.5 cm2/m2 (±5.9) (p = 0.008). CONCLUSION: Presence of respiratory muscle wasting prior to surgery was found to be associated with postoperative respiratory failure.

Sarcopenia after induction therapy is associated with reduced survival in patients undergoing esophagectomy for locally-advanced esophageal cancer.

BACKGROUND: The impact of sarcopenia on the outcome of esophageal cancer patients remains unknown in North American populations. The current study aims to investigate if sarcopenia at the time of esophagectomy for locally-advanced esophageal cancer (LAEC) is associated with survival. METHODS: Patients who underwent induction therapy followed by esophagectomy for LAEC between 2010-2018 at a single institution were identified. Exclusion criteria included follow-up less than 90 days and distant metastatic disease at the time of surgery. Demographic, treatment, and outcome data were retrospectively collected. Computed tomography (CT) scans following induction therapy were analyzed to calculate skeletal muscle index (SMI). Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier and Cox Proportional Hazard regression analysis. RESULTS: Overall, 52 patients met inclusion criteria with a median BMI of 25 (IQR, 22.4-29.1) kg/m2 and age of 65 (IQR, 57-70) years. Sarcopenia was present in 75% (39/52) of patients at the time of surgery. Sarcopenic patients had a lower median BMI and higher median age when compared to non-sarcopenic patients. There was no difference in gender, race, stage, operative technique, post-operative complications, or hospital length of stay between sarcopenic and non-sarcopenic patients. With a median follow-up of 24.9 months, patients with sarcopenia at the time of esophagectomy had worse OS [median 24.3 (IQR, 9.9-34.5) vs. 50.9 (IQR, 25.6-50.9) months, P=0.0292] and DFS [median 11.7 (IQR, 6.4-25.8) vs. 29.4 (IQR, 12.8-26.7) months, P=0.0387] compared to non-sarcopenic patients. CONCLUSIONS: Sarcopenia is associated with reduced overall and DFS in patients undergoing esophagectomy for LAEC.

Relationship between circulating tumor-associated autoantibodies and clinical outcomes in advanced-stage NSCLC patients receiving PD-1/-L1 directed immune checkpoint inhibition.

BACKGROUND: Durable tumor regressions are observed in a subset of advanced-stage non-small cell lung cancer (NSCLC) patients receiving PD-1/-L1 targeted immune checkpoint inhibitors (or 'immunotherapy') alone or in combination with chemotherapy. However, the majority of advanced NSCLC patients receiving these agents do not experience long-term disease control. Existing methods to identify patients most likely to gain clinical benefit from PD-1/-L1 immunotherapy have limitations, creating a need for improved methods to guide treatment selection, particularly for those likely to benefit from single-agent immunotherapy. Here, we describe the development of a series of novel assays for tumor-associated autoantibodies as part of an exploratory study intended to determine if these biomarkers have potential prognostic value in this setting. METHOD: A selection of recombinant tumor autoantigens previously characterized for their diagnostic utility were developed and preliminarily evaluated by this study. These include: Fumarate Dehydrogenase (FH), Hydroxysteroid 17-Beta Dehydrogenase 10 (HSD17B10), Inosine Monophosphate Dehydrogenase 2 (IMPDH2), New York Esophageal Squamous Cell Carcinoma-1 (NY ESO-1), Phosphoglycerate Mutase 1 (PGAM1), and Vimentin. Custom Luminex immunobead assays were developed for these targets to quantitatively assess autoantibody levels in individual patient sera. Assays were erected as indirect immunoassays on MagPlex® Microspheres using standard carbodiimide/NHS-based chemistries, utilizing a biotin-conjugated secondary (i.e. anti-human IgG) antibody and R-phycoerythrin-conjugated streptavidin reporter system. Standard curves were created for quantitative purposes using commercially-available anti-antigen antibodies and permitted analytical performance characteristics to be calculated. These assays were used to preliminarily evaluate a series of pretreatment serum samples from stage IV NSCLC patients receiving anti PD-1/-L1 therapy after failure of at least one prior line of therapy (n = 40) and their classification efficiency calculated based on 12 months overall survival (OS) threshold. RESULTS: Six assays were developed that each showed dynamic ranges of four orders of magnitude and provided more than 90% classification accuracy based on the observed clinical outcome data. Inter- and intra-assay precision was assessed within these standards and overall %CVs of ≤7% and ≤ 10%, respectively, were calculated. Generally, the baseline level of autoantibodies were significantly (p < 0.05) lower in the ≥12 months survival group relative to the <12 months survival groups. Serum titers of FH, HSD170B, NY-ESO-1, and vimentin were significantly correlated with ≥12 month survival (p-value 0.0038, 0.0061, 0.0073, and 0.022, respectively). IMPDH2 and PGAM1 were found to have marginal significance (p-value 0.08 and 0.076, respectively). CONCLUSION: This study demonstrates an efficient and promising means for assessing circulating autoantibody titers that could be useful in selecting advanced NSCLC patients for PD-1/-L1 directed immunotherapy. Further exploration and validation of this paradigm is warranted to further refine current treatment selection methods for this therapeutic strategy.

Infrarenal inferior vena cava agenesis and recurrent deep vein thrombosis: a case report and literature review.

Inferior vena cava agenesis is a rare congenital vascular defect often diagnosed as an incidental finding in asymptomatic patients. When symptoms arise, it can present with chronic venous stasis or unprovoked deep vein thrombosis (DVT). A 42-year-old man with history of unprovoked right lower extremity (RLE) DVTs was admitted for swelling, pain and erythema to the RLE, concerning for new DVT. Venous Doppler ultrasound showed a chronic DVT of the right proximal femoral vein in addition to an acute DVT of the distal femoral vein. Extensive thrombophilia workup was negative and additional imaging with abdominal computed tomography scan revealed the absence of the infrarenal inferior vena cava. Patient was treated with oral anticoagulation and compression stockings and discharged with clinical improvement. At 3-month follow-up, patient was completely asymptomatic. Recurrent unprovoked DVTs in young patients require exhaustive work up including imaging studies to rule out vascular anomalies.

National Comprehensive Cancer Network guidelines compliance of a sarcoma service: A retrospective review.

BACKGROUND: Clinical workup and treatment guidelines have been published by the National Comprehensive Cancer Network (NCCN) to ensure patients are treated uniformly and appropriately. This study sought to retrospectively review patients with a new diagnosis of sarcoma who were treated in a National Cancer Institute (NCI) designated center and determine compliance rates with guidelines for sarcoma. AIM: To evaluate our compliance of NCCN sarcoma guidelines at a major NCI designated center and to report instances of deviation that could be used for future studies to improve patient care. METHODS: Data was collected retrospectively as an internal review and quality assessment of 35 newly diagnosed and treated patients. Demographic data were recorded and information concerning whether patients had appropriate imaging, biopsy and management. Variables of interest were expressed as raw numbers and percentages. RESULTS: Primary site imaging was obtained in 100% of cases. Chest and full-body imaging were obtained in 97% and 100% of indicated cases, respectively. Tissue was obtained preoperatively in 97% of cases. Imaging was reviewed at multidisciplinary Treatment Planning Conference (TPC) in 97% of cases. Pathology was reviewed in 94% of cases in TPC. Both tumor, node, metastasis staging and plan of care were reviewed in 100% of cases in TPC. Treatment guidelines were followed in 94% of cases reviewed. CONCLUSION: This study evaluated the workup and treatment provided by a single NCI designated sarcoma service to a series of patients with pathologies defined with the NCCN sarcoma treatment guidelines. Although adherence to NCCN was reported to be very high future prospective studies are required to investigate whether NCCN guidelines impact patient outcomes.

Perioperative thrombelastography serves as an important assessment tool of transfusion requirements during liver transplantation.

BACKGROUND: Thrombelastography has become increasingly used in liver transplantation. The implications of thrombelastography at various stages of liver transplantation, however, remain poorly understood. Our goal was to examine thrombelastography-based coagulopathy profiles in liver transplantation and determine whether preoperative thrombelastography is predictive of transfusion requirements perioperatively. METHODS: A retrospective review of 364 liver transplantations from January 2013 to May 2017 at a single institution was performed. Patients were categorized as hypocoagulable or nonhypocoagulable based on their preoperative thrombelastography profile. The primary outcome was intraoperative transfusion requirements. RESULTS: Of patients undergoing liver transplantation, 47% (n = 170) were hypocoagulable and 53% (n = 194) were nonhypocoagulable preoperatively. Hypocoagulable patients had higher transfusion requirements compared to nonhypocoagulable patients, requiring more units of packed red blood cells (7 vs 4, P < .01), fresh frozen plasma (14 vs 8, P < .01), cryoprecipitate (2 vs 1, P < .01), platelets (3 vs 2, P < .01), and cell saver (3 vs 2 L, P < .01). Additionally, these patients were more likely to receive platelets and cryoprecipitate in the first 24 hours following liver transplantation (both P < .05). No differences were found between rates of intensive care unit length of stay, 30-day readmission, or mortality. CONCLUSION: Coagulation abnormalities are common among liver transplantation patients and can be identified using thrombelastography. Identification of a patient's coagulation state preoperatively aids in guiding transfusion during liver transplantation. This work serves to better direct clinicians during major surgery to improve perioperative resource utilization. Future prospective work should aim to identify specific thrombelastography values that may predict transfusion requirements.